1. Field of the Invention
This invention relates to filtration of a fluid by means of a filtration device; more particularly, the invention relates to a method and an apparatus for controlling the proportion of a fluid that passes through a filter in a filtration device.
2. Discussion of the Art
All processes for filtering fluids involve three componentsxe2x80x94the fluid itself, a filter, such as, for example, a membrane having a specified porosity, and means to force the fluid through the filter, such as, for example, a pump, gravity, centrifugal force. In some cases, the entire volume of fluid to be filtered is forced through the filter; in these cases, the desired product may be the fluid that has been forced through the filter. In other cases, the purpose of the filtering process is to concentrate a substance present in the fluid; in these cases, the desired product may be the portion of the fluid that has not been forced through the filter. In the latter cases, it may be desirable to control the volume of fluid retained in order to recover a product having a specific concentration of the substance. For example, it may be desired to concentrate, such as, for example, by a factor of 10 to 1, a specific protein dissolved or suspended in a small volume of an aqueous solution.
The conventional method for performing a concentrating operation involves depositing a sample of a fluid in a filter cartridge, such as, for example, a Microcon(copyright) centrifugal filter device, commercially available from Millipore Corporation. The loaded filter cartridge is then placed in a laboratory centrifuge and rotated at a high number of revolutions per minute. The orientation of the filter cartridge in the centrifuge would be such that the xe2x80x9cgxe2x80x9d forces created by the centrifugation operation would tend to drive the fluid through the filter and into a collection container, which is positioned downstream of the filter. The concentration factor is assumed to be a function of the duration of the centrifugation operation; the time required to achieve the desired concentration factor would be estimated by a trained operator. If the desired concentration factor is 10 to 1, then the desired volume retained upstream of the filter of the filter cartridge would be {fraction (1/10)} of the volume initially loaded into the filter cartridge. At the end of the estimated time, the operator would stop the centrifuge and measure the proportion of fluid remaining upstream of the filter of the filter cartridge. If the proportion of fluid remaining upstream of the filter is determined to be approximately correct, the process would be complete. In most cases, however, it would be found that the volume of fluid retained upstream of the filter of the filter cartridge exceeded or fell short of the correct amount. If the volume retained upstream of the filter were too little, correction would be impractical because the concentration of the protein in the protein-containing solution would have been too high. If the volume retained upstream of the filter were too high, another cycle of centrifugation would be performed, with the duration again estimated by the operator in order to provide the desired concentration factor. This method, while effective, is laborious and inexact. If the number of samples to be concentrated at any one time is high, such as, for example, several dozen, the method quickly becomes impractical in a laboratory setting.
Accordingly, it would be desirable to develop a method for separating a solution or suspension into predetermined proportions by a means other than centrifugation, so that the separation can be controlled more accurately. In addition, it would be desirable to develop an automated method for separating a solution or suspension into predetermined proportions so that the proportioning process, once begun, can be performed without the need for an operator. It is further desired to develop a method such that a great number of proportioning processes can be performed simultaneously.
This invention provides an apparatus and a method for dividing a fluid into desired proportions by means of a filtering device. In one aspect, this invention provides a method for dividing a fluid into desired portions, the method comprising the steps of:
(a) providing at least one filtration device, the filtration device comprising a filter;
(b) adding the fluid to the at least one filtration device, the fluid containing material dissolved or suspended therein;
(c) placing the at least one filtration device to which fluid has been added in a pressure vessel, the pressure vessel capable of withstanding a specified level of pressure relative to ambient pressure;
(d) forming a trapped volume downstream of the filter;
(e) increasing the pressure in the pressure vessel upstream of the filter;
(f) allowing a period of time to elapse, the period of time being sufficient to allow the pressure downstream of the filter in the trapped volume to be substantially equal to the pressure upstream of the filter;
(g) unsealing the filtration device; and
(h) venting the pressure vessel.
Optionally, the pressure within the pressure vessel can be reduced before the step (d), the step of forming the trapped volume. The filtration device preferably contains a membrane or barrier having a specified porosity, supported in a housing or in an equivalent element that can be mounted within the pressure vessel.
Many different types of fluids can be filtered by the method of this invention. One type of fluid that is particularly amenable to the method of this invention is a solution containing proteinaceous material dissolved therein. In this type of fluid, the solvent is typically an aqueous solvent.
The operating conditions of this method can be varied widely. For example, the pressure in step (e) can be raised to any pressure that can be withstood by the equipment. Pressures of as high as 215 psia are common in the method of this invention. The pressure in the optional step preceding step (d) can be reduced to as low a level as 0 psia. The pressure can be controlled to allow the division of the fluid into proportions ranging from about 100 to 1 to about 1 to 100. The size of the trapped volume can be varied by various techniques, such as, for example, insertion of plugs or inserts into the volume downstream of the filtration device or removal of plugs or inserts from the volume downstream of the filtration device.
In another aspect, this invention provides an apparatus for dividing a fluid into portions, the apparatus comprising:
(a) a pressure vessel, the pressure vessel capable of withstanding a specified level of pressure relative to ambient pressure;
(b) means for supporting at least one filtration device having a filter;
(c) means for sealing the at least one filtration device, whereby a trapped volume can be created downstream of the filter of the at least one filtration device inserted into the pressure vessel;
(c) means for creating negative pressure or positive pressure or negative and positive pressure relative to ambient pressure within the pressure vessel; and
(d) means for venting the pressure vessel.
Means for sealing (b) include, but are not limited to, rings, gaskets, and similar types of seals. Means for providing negative pressure (c) include, but are not limited to, vacuum pumps. Means for providing positive pressure (c) include, but are not limited to, compressors, pressurized air lines, nitrogen cylinders. Means for providing positive or negative pressure within the pressure vessel further include, but are not limited to, solenoid valves, pneumatic valves, and the like.
The apparatus and method of this invention provide numerous benefits in the field of separating fluids into proportions. These benefits include the following:
(a) providing greater accuracy and repeatability of proportioning operations;
(b) simplifying control of the proportioning operation, i.e., filters may be allowed to remain in the apparatus for an indefinite period of time without any detrimental effect;
(c) providing the capability of performing proportioning operations on a great number of samples simultaneously;
(d) increasing the rapidity of the proportioning operation relative to a centrifugation operation, on account of a lower number of iterations;
(e) enabling complete automation of the proportioning operation after the operation has begun;
(f) providing the capability of varying proportions merely by adjusting the level of vacuum and the level of pressure in the pressure vessel; and
(g) simplifying the introduction of samples into the apparatus and the removal of samples from the apparatus.